Exact dosing times calculations in linear pharmacokinetics

Area of Science:

• Pharmacokinetics
• Computational drug modeling

Background:

• Achieving target drug concentration profiles is crucial for therapeutic efficacy.
• Current methods for calculating dosing time (tau) may lack precision, especially for extravascular dosing.

Purpose of the Study:

• To develop an accurate and automated method for determining dosing time (tau) to control drug concentration fluctuations at steady state (ss).
• To introduce the SSTATE algorithm and software for precise calculation of dosing regimens.

Main Methods:

• Utilized a nested, single-variable root-solving approach with a derivative-free solver for robust calculations.
• Developed the SSTATE algorithm and computer program for automated dosing time and steady-state parameter determination.
• Validated the approach with quinidine dosage regimen calculations and simulation studies.

Main Results:

• The SSTATE program provides exact solutions for dosing time (tau), unlike previous approximation formulas.
• Demonstrated accurate calculation of steady-state parameters including time to peak, maximum, minimum, and mean drug levels.
• Simulation studies revealed significant errors in some prior approximation formulas, particularly for extravascular dosings.

Conclusions:

• The SSTATE program offers a reliable and exact method for calculating optimal dosing times (tau) to manage drug concentration variability.
• This approach enhances the precision of dosage regimen design for both intra- and extravascular administration.
• The findings highlight the limitations of approximation formulas and the advantages of the SSTATE computational method.